3-189957778-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_018192.4(P3H2):c.*134G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 687,132 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.011 ( 15 hom., cov: 31)
Exomes 𝑓: 0.016 ( 100 hom. )
Consequence
P3H2
NM_018192.4 3_prime_UTR
NM_018192.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.666
Genes affected
P3H2 (HGNC:19317): (prolyl 3-hydroxylase 2) This gene encodes a member of the prolyl 3-hydroxylase subfamily of 2-oxo-glutarate-dependent dioxygenases. These enzymes play a critical role in collagen chain assembly, stability and cross-linking by catalyzing post-translational 3-hydroxylation of proline residues. Mutations in this gene are associated with nonsyndromic severe myopia with cataract and vitreoretinal degeneration, and downregulation of this gene may play a role in breast cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
Variant 3-189957778-C-T is Benign according to our data. Variant chr3-189957778-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1198632.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0112 (1701/151920) while in subpopulation SAS AF= 0.0244 (117/4804). AF 95% confidence interval is 0.0208. There are 15 homozygotes in gnomad4. There are 802 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 15 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
P3H2 | NM_018192.4 | c.*134G>A | 3_prime_UTR_variant | 15/15 | ENST00000319332.10 | ||
P3H2 | NM_001134418.2 | c.*134G>A | 3_prime_UTR_variant | 15/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
P3H2 | ENST00000319332.10 | c.*134G>A | 3_prime_UTR_variant | 15/15 | 1 | NM_018192.4 | P1 | ||
P3H2 | ENST00000427335.6 | c.*134G>A | 3_prime_UTR_variant | 15/15 | 1 | ||||
P3H2 | ENST00000490940.1 | n.391G>A | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0112 AC: 1702AN: 151800Hom.: 15 Cov.: 31
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GnomAD4 exome AF: 0.0156 AC: 8334AN: 535212Hom.: 100 Cov.: 6 AF XY: 0.0165 AC XY: 4739AN XY: 287776
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 16, 2019 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at